Heart-rate reactivity and alcohol consumption among sons of alcoholics and sons of non-alcoholics

Abstract

Recent studies have demonstrated that sons of male alcoholics with multigenerational family histories of male alcoholism are characterized by sober heart-rate hyperreactivity to aversive stimuli, susceptibility to alcohol-induced dampening of that hyperreactivity and by increased resting heart rate while intoxicated. Regression analyses indicate that the magnitude of alcohol-induced change in resting and reactive cardiac response is significantly and powerfully associated with the degree of self-reported voluntary alcohol consumption among 85 non-alcoholic males who are either lacking or who have moderate or extensive family histories of male alcoholism. It appears that heightened sensitivity to alcohol-induced increase in resting and decrease in reactive heart rate might mark or underlie familial risk for developing alcoholism.

Full text

Heart-Rate
Reactivity
and
Alcohol
Consumption
Among
Sons
of
Male
Alcoholics
and
Sons
of
Non-Alcoholics
J.B.
Peterson,
Ph.D.',
R.O.
Pihl,
Ph.D.',
J.R.
Seguin,
B.A.',
P.R.
Finn,
Ph.D.2,
S.H.
Stewart,
Ph.D.3
'Departments
of
Psychology
and
Psychiatry,
McGill
University,
Montreal,
Quebec,
2Department
of
Psychology,
Indiana
University,
Bloomington,
Indiana,
3Department
of
Psychology,
McGill
University,
Montreal,
Quebec
Submitted:
January
27,
1993
Accepted:
March
22,
1993
Recent
studies
have
demonstrated
that
sons
of
male
alcoholics
with
multigenerational
family
histories
of
male
alcoholism
are
characterized
by
sober
heart-rate
hyperreactivity
to
aversive
stimuli,
susceptibility
to
alcohol-induced
dampening
of
that
hyperreactivity
and
by
increased
resting
heart
rate
while
intoxicated.
Regression
analyses
indicate
that
the
magnitude
of
alcohol-induced
change
in
resting
and
reactive
cardiac
response
is
significantly
and
powerfully
associated
with
the
degree
of
self-reported
voluntary
alcohol
consumption
among
85
non-alcoholic
males
who
are
either
lacking
or
who
have
moderate
or
extensive
family
histories
of
male
alcoholism.
It
appears
that
heightened
sensitivity
to
alcohol-induced
increase
in
resting
and
decrease
in
reactive
heart
rate
might
mark
or
underlie
familial
risk
for
developing
alcoholism.
Key
Words:
alcohol
abuse,
alcohol
dependance,
alcoholism,
genetics,
children
of
alcoholics,
risk
INTRODUCTION
Alcohol
abuse
and
dependence
are
common,
costly
and
serious
disorders
(Regier
et
al
1990;
Adrian
1984;
Harwood
et
al
1984),
characterized
by
relatively
sporadic,
ineffective
and
expensive
treatments
(Miller
and
Hester
1986).
Alcohol-
ism
has
severe
side-effects,
including
potentiation
of
aggres-
sion
(Pihl
et
al
in
press),
reduction
of
general
productivity,
degeneration
of
mental
and
physical
health
(Adrian
1984;
Harwood
et
al
1984)
and
destruction
of
healthy
social
and
familial
interaction.
Little
is
known
about
the
processes
un-
derlying
the
development
of
alcoholism,
making
the
devel-
opment
and
application
of
treatment
challenging.
However,
the
fact
that
alcoholism
runs
in
families
has
been
established
(Bohman
et
al
1981;
Cadoret
et
al
1980;
Cloninger
et
al
1981;
Goodwin
et
al
1973;
Cotton
1979;
Heath
and
Martin
1988;
Hrubec
and
Omenn
1981)
although
the
manner
in
which
the
familial
predisposition
manifests
itself
has
not
been
deter-
Address
reprint
requests
to:
R.O.
Pihl,
Ph.D.,
Department
of
Psychology,
McGill
University,
1205
Dr.
Penfield
Avenue,
Montreal,
Quebec,
Canada
H3A
1B
1.
mined
(Searles
1988).
In
addition,
a
large
number
of
studies
analyzing
animal
reactions
to
alcohol
have
demonstrated
that
heritable
factors
influence
the
tendency
to
begin
using
alco-
hol
(Deminiere
et
al
1989),
susceptibility
to
alcohol-induced
reinforcement
(McBride
et
al
1990;
George
et
al
1991)
and
development
of
tolerance,
dependence
and
withdrawal
(Crabbe
1989;
Keir
and
Deitrich
1990;
Pihl
and
Peterson
in
press).
Young
sons
of
male
alcoholics
(SOMAs)
appear
to
be
at
particular
risk,
because
of
their
age
(Adrian
1984),
sex
(Helzer
and
Pryzbeck
1988)
and
family
history
(Cloninger
et
al
1981;
Goodwin
1985),
and
often
have
additional
charac-
teristics
which
have
been
linked
independently
to
alcoholism.
SOMAs
are
more
likely
to
suffer
from
conduct
disorder
or
hyperactivity
during
childhood
(Pihl
et
al
1990;
Tarter
et
al
1988).
They
may
also
be
predisposed
to
specific
cognitive
deficits
and
psychophysiological
abnormalities
and
may
react
idiosyncratically
to
alcohol
intoxication
(Pihl
et
al
1990;
Tarter
et
al
1988).
Furthermore,
they
drink
more
alcohol,
take
more
psychoactive
drugs,
are
younger
when
they
begin
using
alcohol
or
drugs
and
suffer
from
more
pathology
related
to
J
PsychiatrNeurosci,
Vol.
18,
No.
4,
1993
190

Heart-rate
reactivity
and
akohol
consumption
alcohol
use
(McCaul
et
al
1990).
Any
or
all
of
these
additional
characteristics
may
underlie
or
mark
the
tendency
to
develop
alcoholism,
in
part
or
in
whole.
The
discovery
of
a
genuine
risk
factor
or
marker
may
aid
in
the
early,
premorbid
identification
of
those
at
great
risk
of
developing
alcoholism
and
abet
attempts
to
prevent
the
development
of
the
full-blown
syndrome.
The
ideal
indicator
might
be
easily
assessed
and
linked
to
the
development
of
alcoholism
in
a
theoretically
plausible
manner-
and
may
be
associated
with
greater
use
of
alcohol
among
individuals
who
are
currently
not
alcoholics.
It
seems
reasonable
to
search
for
such
a
marker
among
those
who
are
at
particularly
high
risk
for
alcoholism,
for
known
but
non-specific
reasons.
The
Douglas
Hospital-McGill
Alcohol
Research
Project
was
de-
signed
with
this
aim
in
mind.
Subjects
participating
in
this
program
are
young
non-alcoholic
SOMAs
with
extensive
multigenerational
family
histories
(MFH)
of
severe
paternal-
line
male
alcohol
dependence
or
abuse.
These
specific
criteria
were
established
for
subject
selection,
in
part
because
indi-
vidual
risk
for
polygenetically
mediated
disorders,
such
as
alcoholism,
clearly
increases
as
a
function
of
the
number
of
that
individual's
affected
relatives
(Gottesman
and
Sheilds
1982).
Adolescent
SOMAs
with
multigenerational
family
histo-
ries
of
alcoholism
appear
comparatively
deficient
in
their
ability
to
abstract
and
plan
and
are
more
likely
to
suffer
from
hyperactivity
or
conduct
disorder
than
control
subjects
matched
for
age,
IQ
and
socioeconomic
status,
free
from
familial
alcoholism
(Harden
and
Pihl
in
press).
This
relative
lack
of
cognitive
capacity
is
also
evident
in
adulthood
(Peter-
son
et
al
1992).
In
addition,
MFH
SOMAs
manifest
an
idiosyncratic
pattern
of
cardiovascular
response
to
various
challenges.
As
pre-adolescents,
they
are
characterized
by
increased
heart
rate
when
sober
and
vasoconstriction
while
completing
mental
arithmetic
tasks
(Harden
and
Pihl
in
press).
As
young
adults,
they
manifest
a
similar
pattern
of
sober
cardiovascular
hyperreactivity
to
threat
of
and
sig-
nalled
electric
shock
(Finn
and
Pihl
1987;
1988;
Finn
et
al
1990;
Stewart
et
al
1992)
Consumption
of
a
legally
intoxicat-
ing
dose
of
alcohol
appears
to
virtually
eliminate
or
dampen
this
cued
shock
reactivity
(Finn
and
Pihl
1987
1988;
Finn
et
al
1990;
Stewart
et
al
1992).
Young
adult
MFH
SOMAs
also
clearly
display
a
comparatively
heightened
increase
in,
or
stimulation
of,
resting
baseline
heart
rate
while
they
are
acutely
and
legally
intoxicated
(Finn
and
Pihl
1987
1988;
Finn
et
al
1990).
These
patterns
of
cardiovascular
response
may
constitute
a
marker
or
risk
factor
for
alcoholism.
For
example,
they
may
be
in
some
way
related
to
the
quantity
of
alcohol
consumed
which
necessarily
increases
before
the
onset
of
alcohol
abuse
or
dependence.
However,
the
nature
of
the
relationship
between
sober
hyperreactivity,
alcohol-induced
dampening,
alcohol-induced
stimulation
of
heart
rate
and
dfinking
behav-
ior
as
such
has
yet
to
be
explored.
The
data
analyses
described
in
this
paper
were
conducted
in
an
attempt
to
redress
this
omission
-
to
determine
the
nature
of
the
association,
if
any
exists,
between
the
cardiovascular
response
patterns
charac-
teristic
of
SOMAs
with
multigenerational
family
histories
of
alcoholism
and
their
non-alcoholic
drinking
behavior.
METHOD
Data
were
collected
during
a
continuous
project
sponsored
by
the
Douglas
Hospital-McGill
University
Alcohol
Re-
search
Project.
Various
aspects
of
this
project
have
been
described
elsewhere,
and
the
data
included
here
were
drawn
from
these
studies
(Finn
and
Pihl
1987;
1988;
Finn
et
al
1990;
Stewart
et
al
1992).
However,
the
analyses
described
in
this
paper,
conducted
on
a
cumulative
data
sample,
were
not
completed,
nor
have
they
been
reported
previously.
Subjects
Data
were
gathered
on
85
non-alcoholic
non-abstinent
males
between
the
ages
of
18
and
40.
Thirty-six
of
the
subjects
had
an
extensive
multigenerational
history
of
severe
male
alcoholism
-
at
minimum,
an
alcohol-dependent
bio-
logical
father,
alcohol-abusing
or
alcohol-dependent
paternal
grandfather
and
alcohol-abusing
or
dependent
paternal
uncle
or
brother.
In
the
authors'
experience,
three-quarters
of
the
paternal
male
relatives
of
the
subjects
with
multigenerational
family
histories
selected
in
this
manner
have
diagnosable
alcohol
dependence
or
abuse.
Sixteen
additional
subjects
had
a
unigenerational
family
history
(UFH)
of
alcohol
depen-
dence,
limited
in
the
past
two
generations
to
the
biological
father.
The
remaining
33
subjects
had
no
family
history
(FH-)
of
alcohol
abuse
or
dependence
among
their
siblings
or
among
relatives
in
the
previous
two
generations.
The
subjects
were
recruited
through
newspaper
and
posted
advertisements,
screened
initially
by
telephone
(for
provi-
sional
determination
of
their
drinking
behavior
and
family
history
of
alcoholism)
and
interviewed
to
screen
for
psychi-
atric
disorders
by
a
qualified
clinician,
using
the
DSM-lI
criteria
(American
Psychiatric
Association
1980).
In
the
case
of
the
subjects
with
an
MFH
or
UFH
of
alcoholism,
who
were
difficult
to
find
and
were
selected
with
the
idea
of
long-term
participation
in
mind,
available
family
members
were
inter-
viewed,
also
using
the
DSM-III
criteria.
Family
members
who
were
unavailable
were
diagnosed
using
the
Family
History
Research
(FHR)
diagnostic
criteria
(Endicott
et
al
1975).
In
the
case
of
FH-
subjects,
who
were
relatively
easy
to
find,
family
members
were
diagnosed
solely
using
the
FHR
diagnostic
criteria.
The
large
number
of
subjects
meant
that
any
FH-
subject
whose
family
history
was
questionable
in
any
relevant
manner
was
immediately
excluded
from
the
study.
All
the
subjects
had
scores
of
5
or
less
on
the
Michigan
Alcoholism
Screening
Test
(Selzer
1971)
and
were
neither
dependent
upon
nor
abused
alcohol,
according
to
the
DSM-
HI
criteria.
The
subjects
whose
mothers
(currently
or
pre-
viously)
had
one
or
more
symptom
of
alcohol
abuse
or
July
1993
191

Journal
of
Psychiatry
&
Neuroscience
dependence,
according
to
the
DSM-III
or
FHR
diagnostic
criteria,
were
excluded
from
the
study,
to
control
for
the
potentially
confounding
effects
of
fetal
alcohol
syndrome.
Subjects
undergoing
treatment
for
any
active
physical
or
psychiatric
condition
were
excluded,
as
were
those
with
a
schizophrenic
disorder
(active
or
in
remission)
or
who
had
first-
or
second-degree
relatives
with
schizophrenia.
All
the
subjects
refrained
from
consuming
alcohol
for
24
hours
and
from
consuming
food
and
beverages
for
four
hours
prior
to
testing.
They
were
not
allowed
to
smoke
during
the
testing
period.
Since
testing
required
approximately
six
hours
(including
recovery
time),
the
subjects
were
assessed
in
the
morning.
The
subjects
were
paid
$5.00
an
hour
for
their
participation.
Procedure
Upon
arrival
at
the
laboratory,
all
the
subjects
were
required
to
read
and
sign
an
informed
consent
form,
were
weighed
and
were
asked
to
complete
a
questionnaire
on
their
age,
education
and
the
frequency
and
quantity
of
their
alcohol
consumption.
Frequency
was
measured
as
the
number
of
occasions
alcohol
was
consumed
per
week,
on
average,
within
the
last
six
months.
Those
who
drank
alcohol
less
than
once
weekly
were
asked
to
estimate
their
monthly
or
yearly
frequency.
Quantity
was
measured
as
estimated
average
number
of
drinks
(one
beer
=
one
mixed
drink
=
one
glass
of
wine)
consumed
per
drinking
occasion.
A
simple,
easy
to
understand
composite
measure
of
drinking
behavior
was
calculated
by
multiplying
the
average
weekly
frequency
by
the
average
quantity
of
alcohol
consumed.
After
the
interview,
each
subject
was
seated
in
a
reclining
chair,
in
a
quiet,
darkened,
comfortable
room,
attached
to
a
polygraph
and
asked
to
relax.
Baseline
measures
of
heart
rate
were
taken
during
the
following
ten
minutes.
After
baseline
measures
were
established,
a
small
concentric
shock
elec-
trode
was
attached
to
the
inside
of
the
subject's
right
elbow,
and
stereo
headphones
were
placed
on
the
subject's
head.
Three
countdown
and
signalled
shock
trials
were
conducted
and
recorded.
The
countdown,
presented
through
stereo
headphones,
consisted
of
the
taped
presentation
of
a
low-fre-
quency
1
s
tone,
followed
by
an
oral
count
from
ten
to
one
and
the
presentation
of
a
second
1
s
tone.
A
1.85
mA
0.25
s
electric
shock,
delivered
through
the
concentric
electrode,
was
administered
at
the
same
time
as
the
second
tone.
Initial
tone
onset
to
shock
offset
took
14
s.
Each
subject
was
then
unhooked
from
the
shock
electrode
and
administered
three
beverages
consisting
of
95%
pure
USP
ethanol
mixed
with
orange
juice
(five
parts
to
one).
Each
subject
was
required
to
consume
these
beverages
within
20
minutes
(random
across-
group
distribution
of
actual
drinking
rate
was
assumed,
within
this
formal
time
constraint).
Fifteen
minutes
later,
each
subject
was
asked
to
relax,
and
the
physiological
record-
ing
procedure
was
repeated.
The
subjects
who
participated
in
the
Douglas
Hospital-
McGill
Alcohol
Research
Project
were
tested
under
the
in-
fluence
of
five
doses
of
alcohol:
0.132
mL
(active
placebo),
0.50
mL,
0.75
mL,
1.00
mL
and
1.32
mL
of
95%
alcohol
per
kg
of
body
weight.
The
latter
three
doses
are
generally
sufficient
to
produce
blood
alcohol
levels
between
0.08
and
0.1
1
(Stewart
et
al
1992).
Doses
of
alcohol
of
this
magnitude
are
rarely
used
in
studies
of
this
type.
Nonetheless,
research
has
indicated
that
alcohol
must
be
administered
in
such
quantities
to
produce
substantive
effects
among
young
social
drinking
males.
It
is
not
until
blood
alcohol
levels
of
0.08
to
0.1
1
are
reached
that
subjects
with
multigenerational
family
histories
have
reliable
and
significant
alterations
in
their
cardiovascular
functioning
(Stewart
et
al
1992).
Further-
more,
male
university
students
with
blood
alcohol
levels
in
the
same
range
have
clinically
significant
reductions
in
their
ability
to
plan
and
for
the
longer-term
consolidation
of
mem-
ory
(Peterson
et
al
1990).
Data
for
these
analyses
were
therefore
drawn
only
from
those
subjects
who
had
been
administered
alcohol
at
doses
of
0.75
mL/kg,
1.00
mL/kg
and
1.32
mL/kg.
Statistical
measures
designed
to
control
for
this
variability
in
alcohol
dose
are
described
in
detail
below.
Determination
of
cardiovascular
variables
Each
subject's
heart
rate
was
assessed
while
they
were
sober
and
while
intoxicated
by
alcohol.
Resting
baseline
measures
were
calculated
as
average
heart
rate
during
the
last
90
seconds
of
the
ten-minute
pre-stimulus
relaxation
period,
during
both
non-drug
and
drug
conditions.
Reactive
mea-
sures,
in
contrast,
were
calculated
as
the
mean
heart
rate
during
signalled
shock
exposures
(from
the
initial
tone onset
to
7
s
after
the
shock
was
administered),
averaged
over
three
trials,
during
both
non-drug
and
drug
conditions.
The
follow-
ing
variables
were
calculated
from
these
basic
measurements:
1.
sober
reactivity
-
percentage
of
change
in
heart
rate
from
sober
baseline
to
sober
signalled
shock;
2.
post-alcohol
reac-
tivity
-
percentage
of
change
in
heart
rate
from
post-alcohol
baseline
to
post-alcohol
signalled
shock;
3.
post-alcohol
dampening
-
alcohol-induced
change
in
signalled
shock
reactivity,
calculated
as
sober
reactivity
minus
post-alcohol
reactivity;
and
4.
post-alcohol
stimulation
-
percentage
of
change
in
baseline
heart
rate,
from
sober
to
post-alcohol
conditions.
These
variables
(change
scores)
were
used
be-
cause
they
could
be
entered
easily
into
multiple
regression
analyses,
as
described
below.
Arithmetic
scores
(change
from
baseline)
were
used
because
the
groups
did
not
differ
in
sober
resting
baseline
heart
rate,
as
described
below.
Percentage
change
scores
were
used
because
they
account
in
part
for
proportion
of
change,
in
contrast
to
standard
difference
scores.
192
VoL
18.,
No.
4,1993

Heart-rate
reactivity
and
alcohol
consumption
Table
1
Means
and
standard
deviations
of
age,
education,
blood
alcohol
level
and
number
of
alcoholic
beverages
per
week
by
group
according
to
self-reports
Age
Education
Blood
alcohol
level
Number
of
alcoholic
(years)
(years
completed)
(%)
beverages
per
week
Group
n
Mean
SD
Mean
SD
Mean
SD
Mean
SD
FH-
33
22.06
4.07
14.33
1.69
0.90
0.020
5.76
4.72
UFH
16
24.31
4.94
13.38
3.12
0.87
0.012
6.00
3.78
MFH
36
23.58
4.70
13.75
2.13
0.93
0.018
8.97
7.07
All
85
23.13
4.54
13.90
2.20
0.91
0.018
7.16
5.85
RESULTS
ening
are
presented
with
the
potentially
confounding
effect
of
dose
variation
covaried
out.
One-way
ANOVAs
revealed
Demographics,
blood
alcohol
levels
and
alcoholic
no
significant
differences
between
the
groups
in
sober
resting
beverages
per
week
baseline
heart
rate
(F(2,82
=
1.74,
p
<
0.18).
In
contrast,
one-way
ANCOVAs
revealed
that
subjects
in
the
three
One-way
analyses
of
variance
revealed
that
the
subjects
groups
differed
significantly
in
sober
reactivity
in
the
three
groups
did
not
differ
significantly
in
mean
age,
(F(2,82)
=
7.94,
p
<
0.0007),
post-alcohol
dampening
years
of
schooling
or
blood
alcohol
level
but
did
differ
in
the
(F(2,82)
=
16.73,
p
<
0.00001)
when
the
insignificant effect
number
of
alcoholic
beverages
they
consumed
per
week
of
dose
variability
(F(1,8
1)
=
0.1
1,
p
<
0.75)
was
covaried
(F(2,82
=
3.13,
p
<0.0488).
Post-hoc
Fisher's
Least
Signifi-
out,
and
in
post-alcohol
stimulation
(F(2,82)
=
9.99,
cant
Difference
test
indicated
that
subjects
with
multi-
p
<
0.0001)
when
the
insignificant
effect
of
dose
variability
generational
family
histories
consumed
significantly
more
(F(
1,81)
=
0.93,
p
<
0.34)
was
covaried
out.
Post-hoc
Fisher's
alcohol
than
the
FH-
controls
(p
<0.05).
Means
and
standard
LSD
indicated
that:
1.
the subjects
with
multigenerational
deviations
for
all
these
variables
are
presented
in
Table
1.
family
histories
were
more
susceptible
to
sober
reactivity
(p
<
0.0001),
post-alcohol
dampening
(p
<
0.0001)
and
post-
Heart-rate
response
and
familial
status
alcohol
stimulation
(p
<
0.001)
than
the
UFH
and
FH-
sub-
jects;
and
2.
the
FH-
subjects
were
more
prone
to
sober
Table
2
presents
the
heart-rate
measures
(means
and
stan-
reactivity
(p
<0.05)
and
post-alcohol
dampening
(p
<
0.05)
dard
deviations)
by
group
for
sober
and
post-alcohol
resting
than
the
UFH
subjects.
baseline
and
signalled
shock
conditions
and
the
derived
(percentage
of
change)
measures
(means
and
standard
devi-
Heart-rate
response:
correlations
ations)
for
sober
and
post-alcohol
reactivity.
Table
3
presents
the
means
and
standard
deviations
of
the
derived
variables
Further
analyses,
conducted
to
assess
the
nature
of
the
post-alcohol
dampening
(sober
reactivity
minus
post-alcohol
relationship
between
each
measure
of
heart
rate,
demon-
reactivity)
and
post-alcohol
stimulation
(percentage
of
strated
significant
correlations
between
sober
reactivity
and
change
in
baseline
heart
rate
from
sobriety
to
intoxication).
post-alcohol
stimulation
(r
=
0.2320,
s
=
0.0326),
post-alco-
Figures
for
post-alcohol
stimulation
and
post-alcohol
damp-
hol
dampening
and
post-alcohol
stimulation
(r
=
0.3929,
Table
2
Measures
of
heart
rate
by
group
for
sober
and
post-alcohol
resting
baseline
and
signalled
shock
conditions
and
derived
percentage
change
measures
for
sober
and
post-alcohol
reactivity
Post-alcohol
Post-alcohol
Post-alcohol
Sober
baseline
Sober
shock
Sober
reactivity
baseline
shock
reactivity
Group
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Mean
SD
Mean
SD
FfH-
69.40
10.60
73.95
10.77
7.02
9.15
72.01
11.17
74.41
10.47
3.76
6.17
UFH
71.77
12.13
71.97
12.54
0.42
7.44
71.40
9.55
74.10
10.79
3.71
5.76
MFH
66.10
10.39
74.06
10.23
13.07
13.24
74.56
12.01
73.82
11.96
-0.93
5.22
All
68.44
10.90
73.62
10.80
8.34
11.70
73.00
11.22
74.10
11.05
1.76
6.10
193
July
1993

Journal
of
Psychiatry
&
Neuroscknce
Table
3
Derived
measures
(means
and
standard
deviations)
for
post-alcohol
dampening'
and
post-alcohol
stimulationb
Post-alcohol
dampening
Post-alcohol
stimulation
Group
Mean
SD
Mean
SD
FH-
3.26
8.36
4.14
9.77
UFH
-
3.30
4.10
0.48
10.72
MFH
14.00
13.45
13.46
12.76
All
6.58
12.31
7.40
12.40
asober
reactivity
minus
post-alcohol
reactivity
bpercentage
change
in
baseline
heart
rate
from
sobriety
to
alcohol
intoxication
s
=
0.0002),
and
sober
reactivity
and
post-alcohol
dampening
(r
=
0.87,
s
=
0.00001).The
strong
correlation
evident
in
the
latter
case
indicates
that
cardiovascular
reactivity
to
signalled
shock
is
reduced
to
zero
among
intoxicated
individuals
in
these
risk
groups,
regardless
of
its
magnitude
in
the
sober
condition.
This
correlation
is
so
strong
that
there
is
no
point
in
treating
the
two
variables
independently.
Post-alcohol
dampening
was
therefore
retained
in
the
course
of
the
remain-
ing
analyses,
in
preference
to
sober
reactivity.
This
prefer-
ence
was
determined
on
theoretical
grounds:
post-alcohol
dampening
is
an
alcohol
effect,
and
it
appears
reasonable
to
posit
that
it
is
the
consequences
of
the
effect
of
alcohol
on
reactivity,
rather
than
the
reactivity
itself,
that
influences
drinking
behavior.
This
issue
is
detailed
in
the
discussion
below.
Heart-rate
response,
family
status
and
number
of
alcoholic
beverages
per
week
Four
additional
statistics
were
calculated
to
help
clarify
the
nature
of
the
relationship
between
risk,
heart-rate
re-
sponse
and
voluntary
weekly
alcohol
consumption.
A
one-
way
ANCOVA
demonstrated
that
subjects
in
the
three
groups
no
longer
differed
in
the
number
of
alcoholic
bever-
ages
consumed
per
week
(FH-
=
6.23,
UFH
=
7.39,
MFH
=
7.92;
F(2,8
1)
=
0.73,
p
<
0.49)
when
the
significant
effect
of
post-alcohol
dampening
(F(1,8
1)
=
5.70,
p
<
0.05)
was
covaried
out.
Similarly,
a
one-way
ANCOVA
revealed
that
the
three
groups
no
longer
differed
in
number
of
alco-
holic
beverages
consumed
per
week
(FH-
=
6.18,
UFH
=
6.90,
MFH
=
8.18;
F(2,81)
=
0.98,
p
<
0.3807)
when
the
significant
effect
of
post-alcohol
stimulation
(F(1,8
1)
=
5.78,
p
<
0.0185)
was
covaried
out.
However,
a
one-way
ANCOVA
demonstrated
that
family
history
remained
significantly
associated
with
post-alcohol
dampening
(FH-
=
3.91,
UFH
=
-2.75,
MFH
=
13.16;
F(2,81)
=
14.76,
p
<
0.00001)
when
the
significant
effect
of
the
number
of
alcoholic
beverages
per
week
(F(1,8
1)
=
5.70,
p
<
0.0193)
was
covaried
out.
Post-hoc
Fisher's
LSD
indi-
cated
that
the
subjects
with
multigenerational
family
histories
remained
more
susceptible
to
post-alcohol
dampening
(p
<
0.0001)
than
the
UFH
and
FH-
subjects
and
that
the
FH-
subjects
remained
more
prone
to
post-alcohol
dampening
(p
<
0.05)
than
the
UFH
subjects.
Likewise,
a
one-way
ANCOVA
revealed
that risk
remained
significantly
associ-
ated
with
post-alcohol
stimulation
(FH-
=
4.86,
UFH
=
1.08,
MFH
=
12.54;
F(2,81)
=
7.00,
p
<
0.0016)
when
the
signifi-
cant
effect
of
alcoholic
beverages
per
week
(F(1,81)
=
5.78,
p
<
0.0185)
was
covaried
out.
Post-hoc
Fisher's
LSD
indi-
cated
that
subjects
with
multigenerational
family
histories
remained
more
susceptible
to
post-alcohol
stimulation
(p
<
0.001)
than
the
UFH
and
FH-
subjects.
Multiple
regression
analyses
indicated
that
familial
his-
tory,
post-alcohol
dampening
and
post-alcohol
stimulation
cumulatively
accounted
for
a
significant
proportion
of
the
variance
in
self-reported
number
of
alcoholic
beverages
con-
sumed
per
week
(R2
=
17.00,
F(3,84)
=
5.53,
p
<
0.002)
and
that
the
independent
contribution
of
each
variable,
with
the
exception
of
risk,
approached
significance.
Additional
multiple
regression
analyses
revealed
that
risk
and
number
of
alcoholic
beverages
consumed
per
week
independently
and
cumulatively
accounted
for
a
significant
proportion
of
the
variance
in
post-alcohol
dampening
(R2
=
22.4,
F(2,84)
=
11.81,
p
<
0.001)
and
post-alcohol
stimulation
(R2
=
18.49
F(2,84)
=
9.30,
p
<
0.001).
Table
4
shows
the
T-values,
probability
levels
and
sequential
and
simple
R2s
for
the
risk
heart
rate
and
alcohol
consumption
variables
for
each
of
these
analyses.
DISCUSSION
The
analyses
described
in
this
paper
demonstrate
that:
1.
sons
of
male
alcoholics
with
extensive
multigenerational
family
histories
of
male
alcoholism
consume
significantly
more
alcohol
on
a
weekly
basis
(according
to
self-reports)
than
males
with
no
familial
alcoholism,
even
when
they
were
specifically
selected
because
they
were
not
alcoholic;
2.
SOMAs
with
multigenerational
family
histories
are
charac-
terized
by
heightened
heart-rate
response
to
signalled
shock
when
sober
(but
not
when
intoxicated)
and
by
heightened
resting
heart
rate
when
intoxicated;
3.
the
relationship
be-
tween
a
familial
history
of
alcoholism
and
drinking
is
sub-
sumed
by
the
relationship
between
alcohol-induced
reduction
(post-alcohol
dampening)
in
reactive
heart
rate,
or
by
alcohol-induced
(post-alcohol)
stimulation
of
the
resting
heart
rate,
but
the
reverse
is
not
true;
and
4.
post-alcohol
dampening
and
post-alcohol
stimulation
account
for
a
large
and
significant
proportion
of
the
variance
in
drinking
behav-
ior
among
subjects
categorized
according
to
their
family
history
of
alcohol
abuse
and
dependence.
What
does
this
pattern
of
results
mean?
The
association
between
extensive
familial
male
alcoholism
and
an
increase
in
alcohol
consumption
may
be
considered
predictable,
given
that
a
family
history
of
alcoholism
is
currently
the
best
single
marker
of
a
risk
of
developing
alcoholism
(with
the
possible
194
VoL
18.,
No.
4,1993

Heart-rate
reactivity
and
alcohol
consumption
Table
4
Regression
analyses:
T-values,
probability
levels
and
sequential
and
simple
R2s.
Interrelation
of
alcoholic
beverages
per
week,
risk,
post-alcohol
dampening
and
post-alcohol
stimulation
Independent
variable
T-value
Probability
Sequential
R2
Simple
R2
Number
of
alcoholic
beverages
per
week
by
risk,
post-alcohol
dampening,
post-alcohol
stimulation
*
intercept
3.10
0.003
*
risk
0.76
0.450
0.063
0.063
*
post-alcohol
dampening
1.91
0.060
0.132
0.117
*
post-alcohol
stimulation
1.93
0.057
0.170
0.112
Post-alcohol
dampening
by
risk,
number
of
alcoholic
beverages
per
week
*
intercept
-2.18
0.033
*
risk
3.36
0.001
0.162
0.162
*
number
of
alcoholic
beverages
per
week
2.55
0.013
0.244
0.117
Post-alcohol
stimulation
by
risk,
number
of
alcoholic
beverages
per
week
*
intercept
-1.39
0.167
*
risk
2.71
0.008
0.119
0.119
*
number
of
alcoholic
beverages
per
week
2.57
0.012
0.185
0.111
exception
of
conduct
disorder).
It
is
evident
that
increased
alcohol
consumption
constitutes
a
necessary,
although
not
sufficient,
precondition
for
the
development
of
alcohol
abuse
or
dependence.
It
is
precisely
for
this
reason
that
it
is
worth-
while
to
search
for
factors
that
are
associated
with,
or
even
predate,
increases
in
alcohol
consumption.
Demonstrating
that
alcohol
dampens
the
increased
shock-
induced
heart-rate
reactivity
characteristic
of
SOMAs
with
multigenerational
family
histories
of
alcoholism
may
be
more
relevant,
in
part
because
it
is
less
predictable
prima
facie,
and
in
part
because
it
has
interesting
theoretical
impli-
cations.
The
sober
cardiovascular
hyperreactivity
of
SOMAs
with
multigenerational
family
histories
has
been
associated
with
inappropriately
exaggerated
physiological
and
psycho-
logical
preparation
for
activity,
in
keeping
with
Obrist's
idea
of
cardiac-somatic
coupling
(Obrist
1976),
and
as
a
potential
consequence
of
abnormal
cognitive/linguistic
processing
(Peterson
and
Pihl
1990).
Such
reactivity
may
be
a
physio-
logical
concomitant
of
activity
in
the
limbic
and
prefrontal
centers
responsible
for
the
processing
of
novel
and/or
threat-
ening
stimuli
(Harden
and
Pihl
in
press;
Peterson
et
al
1992).
Activity
in
these
centers
has
been
associated
with
animal
and
human
behavior
indicative
of
anxiety
(Gray
1982;
1987).
The
consumption
of
a
relatively
large
dose
of
alcohol
reduces
or
dampens
this
reactivity
(Finn
and
Pihl
1987;
1988;
Finn
et
al
1990;
Stewart
et
al
1992).
Levenson
et
al
(1987)
and
Peterson
and
Pihl
(1990)
have
proposed
that
such
dampening
may
prove
anxiolytic,
and
therefore
negatively
reinforcing.
The
anxiolytic
effects
of
alcohol,
comparable
to
those
produced
by
barbiturates
or
benzodiazepines
(Gray
1982;
1987),
ap-
pear
to
be
manifested
through
pharmacological
effects
on
the
functioning
of
the
anxiolytic-sensitive
septal/hippocampal
novelty/threat
detection
system
(Gray
1982;
1987).
It
is
pos-
sible
that
anxiolysis
emerges,
in
part,
as
a
consequence
of
the
effect
of
alcohol
on
GABA,
the
brain's
major
inhibitory
neurotransmitter
(Gray
1982;
1987).
Alcohol
enhances
the
ability
of
GABA
to
open
the
CL-
ion
channel,
at
the
GABA-
benzodiazepine-CL-receptor
complex
and
directly
potenti-
ates
CL-
ion
intake
(Gray
1982;
1987;
Warneke
1991;
Zorumski
and
Isenberg
1991).
These
two
actions
increase
the
firing
rate
of
GABA
neurons
and
enhance
their
inhibitory
action
(Warneke
1991).
The
hippocampus
contains
a
high
concentration
of
GABAergic
neurons,
arranged
in
"recurrent
inhibitory
circuits"
(Gray
1987),
and
alcohol
may
serve
an
anxiolytic
role
by
enhancing
their
functioning.
Individuals
characterized
by
substantially
elevated
sober
reactivity,
such
as
SOMAs
with
multigenerational
family
histories,
may
find
the
reactivity-dampening
effects
of
alco-
hol
comparatively
reinforcing,
because
of
the
increased
con-
trast
they
may
experience
between
their
sober
and
intoxicated
psychophysiological
states.
Such
individuals
may
consume
alcohol
in
greater
amounts
or
with
greater
regularity
over
July
1993
195

Journal
of
Psychiatry
&
Neuroscience
time,
once
they
have
experienced
alcohol's
reactivity-damp-
ening
effects
during
the
course
of
normal
experimentation
with
drinking
(Peterson
and
Pihl
1990).
The
fact
that
alcohol
reactivity-dampening
is
strongly
associated
with
level
of
alcohol
consumption
provides
general
support
for
this
hy-
pothesis.
SOMAs
with
multigenerational
family
histories
of
alco-
holism
are
also
differentially
susceptible
to
alcohol-induced
resting
baseline
heart-rate
acceleration.
This
phenomena
is
equally
interesting
from
theoretical
and
practical
viewpoints.
Ethanol
administration
produces
an
increase
in
resting
heart
rate
consistently
(Sher
1987)
and
reliably
(Newlin
and
Thom-
son
1990).
Similar
forms
of
increases
in
heart
rate
have
been
associated
with
excitation
of
the
behavioral
activation
(Gray
1982;
Fowles
1980;
1983)
or
psychomotor
exploratory
sys-
tem.
Such
excitation
may
constitute
the
biological
basis
for
increased
incentive
and/or
reward
(Gray
1982;
Fowles
1980;
1983).
Many,
if
not
all,
drugs
with
the
potential
for
abuse
share
psychomotor-stimulant
and
associated
rewarding
prop-
erties
(Wise
and
Bozarth
1987;
Wise
1988).
Alcoholics,
in
fact,
have
comparatively
pronounced
baseline
heart-rate
in-
creases
while
acutely
intoxicated
(Kaplan
et
al
1985;
McCaul
et
al
1989),
and
such
increases
may
be
predictive
of
craving
for
alcohol
(Kaplan
et
al
1985;
Laberg
and
Ellertsen
1987)
and
preference
for
alcohol
reward
(Kaplan
et
al
1983).
Pihl
and
Peterson
(in
press)
have
hypothesized
that
a
dopamine-
mediated,
psychomotor-stimulant-like
response
to
alcohol
may
underlie
this
heart-rate
increase.
Alcohol
is
certainly
capable
of
stimulating
the
dopaminergic
system
(Pihl
et
al
in
press).
The
firing
rate
of
ventral
tegmental
dopaminergic
neurons
increases
upon
exposure
to
non-sedating
doses
of
alcohol,
and
these
neurons
appear
to
mediate
theoretically
rewarding
behavioral
activation
induced
by
psychomotor
stimulant
drugs
(Gessa
et
al
1985).
Various
rat
strains
bred
for
differential
response
to
alcohol
(including
preference)
have
distinctive
patterns
of
sober
and
intoxicated
dopaminergic
function
(Deminiere
et
al
1989;
McBride
et
al
1990)
and
vary
greatly
in
sensitivity
to
the
psychomotor
stimulant
properties
of
alcohol
(Ehlers
et
al
1991).
Such
sensitivity
appears
to
be
strongly
influenced
by
genetic
fac-
tors
(Dudek
et
al
1991).
People
with
high
heart
rates
after
alcohol
consumption
(such
as
SOMAs
with
multigeneratio-
nal
family
histories)
may,
in
fact,
be
more
sensitive
to
etha-
nol-induced
reward.
This
increased
reward,
attendant
upon
intoxication,
may
provide
powerful
reinforcement
for
alco-
hol
consumption
and
lead
to
increases
in
such
consumption
over
time.
This
study,
in
fact,
demonstrates
that
increased
heart
rate
is
associated
with
increased
alcohol
consumption,
at
least
among
certain
(non-alcoholic)
individuals.
It
might
be
argued
that
differences
in
post-alcohol
damp-
ening
and
post-alcohol
stimulation
are
a
consequence
of
initial
differences
in
alcohol
consumption
-
that
it
is
in
fact
the
increased
alcohol
intake
of
the
SOMAs
with
multigenera-
tional
family
histories that
accounts
for
their
characteristic
pattern
of
heart-rate
response.
However,
controlling
for
vari-
ability
in
post-alcohol
dampening
or
post-alcohol
stimulation
virtually
eliminates
the
relationship
between
familial
risk
and
the
level
of
alcohol
consumption.
In
contrast,
controlling
for
variability
in
alcohol
consumption
significantly
reduces
the
degree
of
relationship
between
post-alcohol
dampening
or
post-alcohol
stimulation
and
familial
risk,
but
comes
nowhere
near
eliminating
it.
This
pattern
of
results
means
that
there
is
little
relationship
between
familial
risk
and
alcohol
consumption
in
the
absence
of
variability
in
cardiac
response,
and
that
there
is
still
a
profound
relationship
between
familial
risk
and
cardiac
response,
in
the
absence
of
variability
in
alcohol
consumption.
This
does
not
prove
that
there
is
a
causal
connection
between
post-alcohol
dampening
or
post-
alcohol
stimulation
and
level
of
alcohol
consumption,
but
it
moves
the
idea
beyond
the
level
of
pure
speculation.
In
addition,
it
is
evident
that
relevant
variability
in
cardiac
response
is
not
merely
a
consequence
of
drinking
behavior.
Furthermore,
the
multiple
regression
analyses
presented
in
this
paper
not
only
demonstrate
that
post-alcohol
dampen-
ing
and
post-alcohol
stimulation
are
powerful
predictors
of
alcohol
consumption,
but
that
they
are
better
predictors
than
family
history
-
one
of
the
two
best
predictors
of
alcoholism
known
to
date
(Pihl
et
al
1990)
-
even
when
the
potential
predictive
power
of
a
family
history
of
alcoholism
has
been
purposefully
exaggerated
through
extremely
careful
subject
selection.
This
means
that
post-alcohol
dampening
and
post-
alcohol
stimulation
may
be
used
to
successfully
identify
individuals
within
a
known
risk
group
who
are
most
likely
to
engage
in
the
one
form
of
behavior
-
the
consumption
of
alcohol
-
which
necessarily
precedes
development
of
alco-
holism.
In
addition,
post-alcohol
dampening
and
post-alco-
hol
stimulation
are
easy
to
measure
and
play
a
theoretically
plausible
role
in
marking
susceptibility
to
alcohol-induced
negative
reinforcement
and
reward.
The
influence
of
various
methodological
problems
poten-
tially
complicate
interpretation
of
the
familial
risk/cardiac
reactivity/alcohol
consumption
relationship,
as
described
in
this
study,
contributing
what
might
be
substantial
non-sys-
tematic
error
to
the
data.
Data
from
self-reports
on
alcohol
use,
for
example,
have
been
criticized
for
their
susceptibility
to
social
desirability
bias
(Babor
et
al
1990).
This
criticism
is
based
on
the
assumption
that
those
who
abuse
substances,
in
particular,
may
under-report
the
degree
of
their
substance
use.
However,
there
is
no
compelling
evidence
to
support
this
view.
A
recent
review
of
the
literature
by
Sobell
and
Sobell
(1990)
concludes
that
self-reports
generally
provide
accurate
estimates
of
alcohol
use,
even
among
alcohol
abusers,
who
may
be
considered
motivated
to
falsify
their
responses
to
conform
with
social
demand.
Subjects
in
this
study,
in
con-
trast,
were
selected
for
their
relative
sobriety
and
had
no
reason
to
be
ashamed
of
their
essentially
normative
patterns
of
alcohol
use.
Furthermore,
all
the
subjects
were
questioned
while
sober,
under
laboratory
conditions,
and
answered
ques-
tions
regarding
alcohol
use
in
a
non-threatening
context:
in
a
brief
questionnaire
for
assessing
demographic
information.
196
VoL
18,
No.
4,1993

July
1993
Heart-rate
reactivity
and
alcohol
consumption
197
The
validity
of
self-report
data
is
demonstrably
enhanced
under
such
circumstances
(Babor
et
al
1990;
Sobell
and
Sobell
1990;
Baker
and
Brandon
1990).
The
use
of
change
scores
also
inevitably
adds
error
to
the
analyses.
A
variable
constructed
from
the
arithmetic
combination
of
two
variables
retains
the
error
of
both.
It
is
possible,
therefore,
that
rela-
tively
imprecise
measures
of
cardiac
response
were
used
to
predict
inexact
self-reports
of
alcohol
consumption.
In
addi-
tion,
three
different
doses
of
alcohol
were
used
to
induce
changes
in
cardiac
response,
and
the
post-hoc
statistical
control
(ANCOVA)
instituted
to
restrict
the
effect
of
this
a
priori
dose
differential
is
imperfect.
These
methodological
shortcomings
undoubtedly
reduce
the
accuracy
of
these
findings
by
adding
potentially
control-
lable
random
error.
However,
it
is
important
to
note
that
the
addition
of
such
error
in
fact
reduces,
rather
than
increases,
the
probability
of
detecting
statistically
significant
relation-
ships
of
the
nature
described
above.
It
is
therefore
reasonable
to
conclude
that
post-alcohol
dampening
and
post-alcohol
stimulation
are
strongly
associated
with
levels
of
alcohol
consumption
(although
they
cannot
be
attributed
to
that
con-
sumption),
even
when
imperfectly
assessed
and
correlated
with
relatively
inaccurate
estimates
of
drinking
behavior.
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